title: New insights into the role of glycogen synthase kinase-3 in Alzheimer's disease.
abstract: BACKGROUND
  Glycogen synthase kinase-3 (GSK-3) is recognized as a crucial player in many cellular functions and its activity is tightly controlled by complex mechanisms that are each dependent upon specific signaling pathways. Furthermore, GSK-3 dysfunction has been linked to a number of pathologies, including Alzheimer's disease (AD). In particular, the involvement of GSK-3 in several key pathophysiological pathways leading to AD and neurodegenerative diseases has placed this enzyme in a central position in this disorder.
  
  
  METHODS
  This article offers a review of the relationship between GSK-3 and AD with a special focus on recent evidence showing a key role of GSK-3 activity in modulating cellular pathways controlling amyloid formation, especially through the control of β-site APP-cleaving enzyme 1 gene expression, as well as its role as a key regulator of neurogenesis.
  
  
  CONCLUSIONS
  GSK-3 appears to be a cellular nexus, integrating several signaling systems, including several second messengers and a wide selection of cellular stimulants. The next few years will certainly bring us further insights into the cellular functions of this fascinating enzyme and its potential as a therapeutic target in AD and other neurological disorders.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Valderrebollo 5, 28041-Madrid , Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Medina
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D055495:Neurogenesis; D011499:Protein Processing, Post-Translational
chemical_list: D016564:Amyloid beta-Protein Precursor; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053829:Amyloid Precursor Protein Secretases